J. Barbarino, D. Kroetz, R. Altman
May 1, 2014
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0
Influential Citations
6
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Journal
Pharmacogenetics and Genomics
Abstract
Abacavir is a nucleoside reverse transcriptase inhibitor (NRTI) used for treatment of HIV infection. HIV infection is usually treated with antiretroviral therapy regimens, which consist of three or more different drugs used in combination. Typical antiretrovirals used in these regimens include NRTIs, non-NRTIs, protease inhibitors, and integrase strand inhibitors [1]. Abacavir makes an ideal addition to these types of combination therapies because of its dosing flexibility. It can be administered either once or twice a day to match the dosing pattern of other drugs and can also be administered as tablets that contain other antiretroviral drugs such as lamivudine and zidovudine, allowing for a reduction in pill count [2]. Abacavir is generally well tolerated, and common side effects include nausea, headache, and diarrhea [2]. However, ~ 5–8% of patients experience a hypersensitivity reaction (HSR) within the first 6 weeks of treatment. Symptoms of an HSR include at least two of the following: fever, rash, cough, gastrointestinal symptoms, dyspnea, and fatigue [3]. These symptoms worsen with continued treatment, but typically improve within 24 h after discontinuation. However, drug rechallenge after discontinuation of abacavir because of an HSR can result in symptom recurrence within a matter of hours, and can lead to immediate and potentially fatal allergic reactions [4,5]. This hypersensitivity reaction is strongly linked to the presence of the HLA-B*57:01 allele, and testing for the allele before abacavir treatment is recommended by the US Food and Drug Administration (FDA) [6], the European Medicines Agency [7], the Clinical Pharmacogenetics Implementation Consortium [3], and the Dutch Pharmacogenetics Working Group [8]. Abacavir was also reported to be associated with a higher risk for myocardial infarction as compared with other NRTIs [9–12]. However, a meta-analysis carried out by the FDA in 2012 failed to find any such association [13].